DESCRIPTION (modified from applicant's abstract) This project focuses on spontaneous elevations of intracellular calcium in growth cones (calcium waves) that regulate extension of neurites. The outgrowth of neurites to establish specific neuronal connections is an important aspect of early development of the nervous system. The research addresses the mechanisms of generation of calcium waves in growth cones of amphibian spinal neurons in culture and has two major specific aims. The first aim is to investigate the contributions of a potentially novel calcium leak pathway in combination with known calcium transporters to the generation of calcium waves. The second aim is to determine the identify and roles of intracellular calcium stores in amplifying elevations of intracellular calcium in growth cones and thereby regulating neurite extension. Optical imaging of intracellular calcium and recording of ionic currents will be used to address these aims.